PPT1 (palmitoyl-protein thioesterase 1) is a lysosomal enzyme that catalyzes the depalmitoylation of S-palmitoylated proteins, removing palmitate groups from cysteine residues to regulate protein stability and localization 1. PPT1 demonstrates substrate specificity for palmitoylated proteins and palmitoylcysteine, distinguishing it from PPT2 1. The enzyme plays critical roles in multiple cellular processes by modulating protein palmitoylation status. PPT1 regulates NLRP3 inflammasome activation by controlling NLRP3 protein stability through depalmitoylation, with PPT1 inhibition leading to increased NLRP3 palmitoylation and enhanced inflammatory responses 2. In angiogenesis, PPT1 modulates Gpx1 protein stability through depalmitoylation, with PPT1 deficiency resulting in reduced pathological angiogenesis 3. PPT1 also regulates autoimmune responses by depalmitoylating TLR9, facilitating its release from UNC93B1 and promoting inflammatory cytokine production 4. Disease relevance includes mutations causing neuronal ceroid lipofuscinosis type 1 (CLN1), a severe neurodegenerative disorder characterized by motor decline, epilepsy, and visual loss 5. Clinically, PPT1 represents a therapeutic target, with inhibitors like GNS561 showing efficacy against hepatocellular carcinoma through lysosomal dysfunction and autophagy blockade 6.